Cyclic Dipeptides. 3. Synthesis of Methyl (R)-6-[(tert-Butoxycarbonyl)amino]-4,5,6,7-tetrahydro-2-methyl-5-oxo-1,4-thiazepine-3-carboxylate and Its Hexahydro Analogs. Elaboration of a Novel Dual ACE/NEP Inhibitor

Synthetic routes to highly functionalized 1,4-thiazepinones 2 and 3 have been developed. S-Ac-NBOC-L-Cys-D(L)-ThrOMe 7a,b have been prepared and, after transformation into the corresponding mesylates, used as the cyclization substrates. Treatment of these compounds with LiA1H(OMe)3 in THF results in mesylate elimination and thiolacetate reduction, giving rise to both a Michael acceptor (α,β-unsaturated ester) and Michael donor (thiol anion), which undergo in situ intramolecular conjugate addition leading to the stereoselective formation of only two of the four possible stereoisomers of 2. On the other hand, PCC/CaCO3 oxidation of 7a gave in 80% yield the corresponding ketone 11, which was in turn transformed into the enol triflate 15. Cleavage of the thiolacerate moiety, simultaneous elimination of trifluoromethanesulfonic acid to generate an allene system, and addition of the thiol group to the central carbon of the allene to provide the enantiomerically pure cyclic compound 3 in 85% yield was effected via a one- pot reaction by means of MeONa/MeOH. Thiazepinone 3 is an interesting intermediate for the preparation of conformationally restricted dipeptide mimetics, and its elaboration into the dual ACE/NEP inhibitor 4 is reported

Cyclic Dipeptides - A Stereocontrolled Synthesis of (2s,3r,6r) and (2r,3r,6r)-6-tert-butoxycarbonylamino-3-methoxycarbonyl-2-methyl-5-oxope Rhydro-1,4-thiazepine

A stereselective synthesis of the title compounds, starting from commercially available amino acids, is described. The absolute stereochemistry of 3a and 3b has been deduced on the basis of H-1 NMR and chemical degradation studies. The formation of only these two isomers has been rationalized in terms of molecular mechanics calculations

The deep-water rose shrimp in the Ionian Sea: a spatio-temporal analysis of zero-inflated abundance data

In the ecological field, the sampling of abundance data is often characterized by the zero inflation of population distributions. Constrained zero-inflated GAM’s (COZIGAM) are obtained assuming that the probability of non-zero inflation and the mean non-zero-inflated population abundance are linearly related. Models of this class have been applied to a spatio-temporal case study concerning the deep-water rose shrimp, Parapenaeus longirostris (Lucas, 1846). Abundance data were collected during 16 experimental trawl surveys conducted from 1995 to 2010 in the Ionian Sea. The sampling design adopted was random-stratified by depth, with proportional allocation of hauls to the area of each depth range and geographical sector. Density index (N/km2) and length (mm) were considered for each haul identified by time, depth, geographic coordinates and geographical sector

Anthropogenic impact in the Santa Maria di Leuca cold-water coral province (Mediterranean Sea): observations and conservation straits

The Santa Maria di Leuca (SML) cold-water coral (CWC) province is a proposed priority conservation area according to several conservation initiatives in the Mediterranean Sea. Part of it is a Fisheries Restricted Area (FRA). Anthropogenic impacts due to fishing on this FRA were investigated using a towed camera system during 2005. The geographic distribution of fishing effort in the SML CWC province was examined through an observers' program of longline and trawl fishing activities during 2009 and 2010 and Vessel Monitoring by satellite System (VMS) data from 2008 to 2013. Using the video system, it was possible to observe evidence of impacts in the FRA due to longlines, proved by remains of lines on the bottoms and/or entangled in corals, and those due to trawl nets, proved by trawl door scars on the bottom. The application of Generalized Liner Models indicates that the impacts due to longline were significantly related to a geographic site characterized by carbonate mounds while those from trawl net were significantly related to the soft bottoms, consisting of bioturbated fine-grained sediments. The presence of waste of various types was also observed in the FRA; plastic was the most widespread waste and was significantly related to a macrohabitat characterized by the presence of corals. The geographic distribution of fishing effort for each type of fishing were rather superimposed in the two years of the observers' program and six years of VMS data with a significantly greater fishing effort outside the FRA than inside this area. The trawlers generally fished on the muddy bottoms of the upper and middle slope within the SML CWC province and near and inside the northward limit of the FRA. The longliners fished mainly on the shelf in north and off the FRA. The coral by-catch was only recorded during 2009 in 26% of the trawl hauls. No coral by-catch was recorded from longlining in either year. The catches from longlining mainly consisted of Chelidonichthys lucerna, Merluccius merluccius and Conger conger while those from trawling mostly consisted of Aristeus antennatus, Aristaeomorpha foliacea and M. merluccius. The information collected during the observers' program and VMS data indicated greater impact due to trawling than longlining. The conservation and effective management of this vulnerable marine ecosystem remain difficult

An eco-epidemiological model supporting rational disease management of Xylella fastidiosa. An application to the outbreak in Apulia (Italy)

Knowledge on the dynamics of Xylella fastidiosa infection is an essential element for the effective management of new foci. In this study, we propose an Eco-epidemiological Model (XEM) describing the infection dynamics of X. fastidiosa outbreaks. XEM can be applied to design disease management strategies and compare their level of efficacy. XEM is a spatial explicit mechanistic model for short-range spread of X. fastidiosa considering: i) the growth of the bacterium in the host plant, ii) the acquisition of the pathogen by the vector and its transmission to host plants, iii) the vector population dynamics, iv) the dispersal of the vector. The model is parametrized based on data acquired on the spread of X. fastidiosa subsp. pauca in olive groves in the Apulia region. Four epidemiological scenarios were considered combining host susceptibility and vector abundance. Eight management strategies were compared testing several levels of vector control efficacy, plant cutting radius, time to detection and intervention. Simulation results showed that the abundance of the vector is the key factor determining the spread rate of the pathogen. Vector control efficacy and time to detection and intervention emerged as the key factors for an effective eradication strategy. XEM proved to be a suitable tool to support decision making for the drafting and management of emergency plans related to new outbreaks

Party hard: Drug-related fatalities in Ibiza from 2010 to 2016

IntroductionIllicit drug use is well known as an important contributor to the global burden of diseases, but the physical and psychopathological risks of recreational drugs misuse are often underestimated and drug-related fatalities in specific settings are under-investigated.Objectives and methodsIn the framework of the EU-funded project “EU-Madness”, we collected and analysed all the reports of drug-related fatalities in Ibiza from January 2010 to September 2016, with the aim of characterising the sample, and identifying the involved substances and the nature of deaths associated with their consumption.ResultsOverall, 58 drug-related fatalities were registered from 2010 to September 2016 (87.9% males, 12.1% females, mean age 33.16; females were significantly younger than males). Most of the deceased were Britons (36.2%), followed by Spanish (22.4%), Italians (6.9%) and Germans (5.2%). In half the cases, the substance identified in post-mortem analyses was a stimulant; in 24.1% of the sample it was a depressor a prescription drug or more than two substances in 22.4%. Most of the fatalities were due to cardiovascular accidents (62%); 22.4% were deaths by drowning, 12% by fall from heights and 3.4% were due to mechanical asphyxia.ConclusionsAccording to the results from our sample, stimulants (mainly MDMA and cocaine) are the substances of abuse involved in most drug-caused fatalities. The number of fatalities per year has been steadily increasing, but the growing diffusion of novel psychoactive substances (NPS) does not seem to be a direct cause (although better methods of their analysis in post-mortem samples should be designed).Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec

LE PROSPETTIVE DELLO SVILUPPO UMANO E DELLE CAPACITAZIONI: LE DIMENSIONI PEDAGOGICHE DI UN INCONTRO TRA SOSTENIBILITA' E CAPABILITIES

Il presente contributo è frutto di un lavoro collettaneo realizzato nell'ambito del Laboratorio "La prospettiva dello Sviluppo Umano e delle capacitazioni all'interno della Siref Summer School 2020. Attraverso tre passaggi "chiave" quali le prospettive pedagogiche di un incontro tra sostenibilità e capabilities, il discorso sulla sostenibilità come "paradigma pedagogico" e il discorso sull'educazione come "cura", fornisce una possibile lettura circa le nuove fragilità, dovute anche all'emergenza pandemica, e una prospettiva futura, ma auspicabile anche nel preesente, in cui si assuma la cultura della sostenibilità anche e soprattutto come cultura di un primato educativo che ridisegni il senso e il carattere dell'idea di comunità con un'impronta etica , democratica e di emancipazion